Murine models have been extensively utilized by Washington University Digestive Diseases Research Core Center investigators and are central to DDRCC biomedical research into diverse aspects of the digestive system in development, health, and disease. The Murine Models and Gnotobiotics Core has been and will continue to be dedicated primarily to producing and maintaining genetically altered animals and to providing, deriving, and manipulating gnotobiotic mice for DDRCC members in a timely, reliable, and cost-effective manner. In addition, the Core provides ancillary services for maintaining mouse pedigrees, such as assisted reproduction, as well as rapid transfer of mutations or transgenes from one genetic background to another using speed congenics. We will continue to offer these services in the next project period. New services to be offered include the maintenance of a Mouse Bank that will house and provide Cre and doxycycline-inducible transgenic mice of use to DDRCC members and the implementation of new, state-of-the-art methods for generating knockout and knockin mice. The Aims include: (1) Generation and propagation of transgenic, knockout, and chimeric mice for the study of digestive diseases. This includes injections of DNA into zygotes and of ES cells into blastocysts and morulae, as well as assistance with breeding, colony maintenance, rederivation of lines as specific pathogen-free, and in vitro fertilization; (2) Movement of specific alleles onto defined strain backgrounds by a speed congenic approach; (3) Maintenance of a Mouse Bank containing transgenic strains of use to DDRCC investigators; (4) Provision of unmanipulated germ-free mice and genotypically matched conventionally-raised control animals; (5) Colonization of germ-free mice with bacteria; (6) Rederivation of germ-free mice from existing conventionally-raised strains of genetically modified mice.